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https://www.readbyqxmd.com/read/28340683/trpv4-moves-toward-center-fold-in%C3%A2-rosacea-pathogenesis
#1
Yong Chen, Carlene D Moore, Jennifer Y Zhang, Russell P Hall, Amanda S MacLeod, Wolfgang Liedtke
Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 a translational-medical target in rosacea. However, signaling mechanisms causing increased expression of TRPV4 await elucidation. Moreover, we ask whether TRPV4-mediated Ca(++)-influx evokes mast cell degranulation.
April 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#2
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28303089/protease-activated-receptor-2-par2-induces-long-term-depression-in-the-hippocampus-through-transient-receptor-potential-vanilloid-4-trpv4
#3
Efrat Shavit-Stein, Avital Artan-Furman, Ekaterina Feingold, Marina Ben Shimon, Zeev Itzekson-Hayosh, Joab Chapman, Andreas Vlachos, Nicola Maggio
Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of N-methyl-D-aspartate receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28295351/when-size-matters-transient-receptor-potential-vanilloid-4-channel-as-a-volume-sensor-rather-than-an-osmo-sensor
#4
Trine L Toft-Bertelsen, David Krízaj, Nanna MacAulay
Transient receptor potential channel 4 of the vanilloid subfamily (TRPV4) is activated by a diverse range of molecular cues, such as heat, lipid metabolites, synthetic agonists, in addition to hyposmotic challenges. As a non-selective cation channel permeable to Ca(2+) , it transduces physical stress in the form of osmotic cell swelling into intracellular Ca(2+) -dependent signaling events. Its contribution to cell volume regulation might include interactions with aquaporin (AQP) water channel isoforms, although the proposed requirement for a TRPV4-AQP4 macromolecular complex remains to be resolved...
March 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28284871/pharmacological-evaluation-of-novel-6-aminopyridin-3-yl-4-pyridin-2-yl-piperazin-1-yl-methanone-derivatives-as-trpv4-antagonists-for-the-treatment-of-pain
#5
Naoki Tsuno, Akira Yukimasa, Osamu Yoshida, Shinji Suzuki, Hiromi Nakai, Tomoyuki Ogawa, Motohiro Fujiu, Kenji Takaya, Azusa Nozu, Hiroki Yamaguchi, Hidetoshi Matsuda, Satoko Funaki, Natsue Yamanada, Miki Tanimura, Daiki Nagamatsu, Toshiyuki Asaki, Narumi Horita, Miyuki Yamamoto, Mikie Hinata, Masahiko Soga, Masayuki Imai, Yasuhide Morioka, Toshiyuki Kanemasa, Gaku Sakaguchi, Yasuyoshi Iso
A novel series of (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives were identified as selective transient receptor potential vanilloid 4 (TRPV4) channel antagonist and showed analgesic effect in Freund's Complete Adjuvant (FCA) induced mechanical hyperalgesia model in guinea pig and rat. Modification of right part based on the compound 16d which was disclosed in our previous communication led to the identification of compound 26i as a flagship compound. In this paper, we described the details about design, synthesis and structure-activity relationship (SAR) analysis at right and left part of these derivatives (Fig...
March 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28283888/kinin-receptors-sensitize-trpv4-channel-and-induce-mechanical-hyperalgesia-relevance-to-paclitaxel-induced-peripheral-neuropathy-in-mice
#6
Robson Costa, Maíra A Bicca, Marianne N Manjavachi, Gabriela C Segat, Fabiana Chaves Dias, Elizabeth S Fernandes, João B Calixto
Kinin B1 (B1R) and B2 receptors (B2R) and the transient receptor potential vanilloid 4 (TRPV4) channel are known to play a critical role in the peripheral neuropathy induced by paclitaxel (PTX) in rodents. However, the downstream pathways activated by kinin receptors as well as the sensitizers of the TRPV4 channel involved in this process remain unknown. Herein, we investigated whether kinins sensitize TRPV4 channels in order to maintain PTX-induced peripheral neuropathy in mice. The mechanical hyperalgesia induced by bradykinin (BK, a B2R agonist) or des-Arg(9)-BK (DABK, a B1R agonist) was inhibited by the selective TRPV4 antagonist HC-067047...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28274924/dynamic-coupling-between-trpv4-and-ca-activated-sk1-3-and-ik1-k-channels-plays-a-critical-role-in-regulating-the-k-secretory-bk-channel-in-collecting-duct-cells
#7
Yue Li, Hongxiang Hu, Jin-Bin Tian, Michael X Zhu, Roger G O'Neil
The large conductance Ca2+-activated K+ channel, BK (KCNMA1), is expressed along the connecting tubule (CNT) and cortical collecting duct (CCD) where it underlies flow- and Ca2+-dependent K+ secretion. Its activity is partially under the control of the mechanosensitive TRPV4 Ca2+-permeable channel. Recently we identified three small/intermediate conductance Ca2+-activated K+ channels, SK1 (KCNN1) and SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca2+-binding affinities, that are expressed in CNT/CCD and may be regulated by TRPV4-mediated Ca2+ influx...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28274876/hypotonic-stress-promotes-atp-release-reactive-oxygen-species-production-and-cell-proliferation-via-trpv4-activation-in-rheumatoid-arthritis-rat-synovial-fibroblasts
#8
Fen Hu, Zhenhai Hui, Wei Wei, Jianyu Yang, Ziyuan Chen, Bu Guo, Fulin Xing, Xinzheng Zhang, Leiting Pan, Jingjun Xu
Rheumatoid arthritis (RA) is a chronic and systemic autoimmune-disease with complex and unclear etiology. Hypotonicity of synovial fluid is a typical characteristic of RA, which may play pivotal roles in RA pathogenesis. In this work, we studied the responses of RA synovial fibroblasts to hypotonic stress in vitro and further explored the underlying mechanisms. Data showed that hyposmotic solutions significantly triggered increases in cytosolic calcium concentration ([Ca(2+)]c) of synoviocytes. Subsequently, it caused rapid release of ATP, as well as remarkable production of intracellular reactive oxygen species (ROS)...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28249987/trpv4-ion-channel-is-a-novel-regulator-of-dermal-myofibroblast-differentiation
#9
Shweta Sharma, Rishov Goswami, Michael Merth, Jonathan Cohen, Kai Y Lei, David X Zhang, Shaik O Rahaman
Scleroderma is a multisystem fibroproliferative disease with no effective medical treatment. Myofibroblasts are critical to the fibrogenic tissue repair process in the skin and many internal organs. Emerging data support a role for both matrix stiffness, and transforming growth factor β1 (TGFβ1), in myofibroblast differentiation. Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel activated by both mechanical and biochemical stimuli. The objective of this study was to determine the role of TRPV4 in TGFβ1- and matrix stiffness-induced differentiation of dermal fibroblasts...
March 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28244642/carbenoxolone-inhibits-trpv4-channel-initiated-oxidative-urothelial-injury-and-ameliorates-cyclophosphamide-induced-bladder-dysfunction
#10
Xiling Zhang, Shan Gao, Masayoshi Tanaka, Zhen Zhang, Yanru Huang, Takahiko Mitsui, Manabu Kamiyama, Schuichi Koizumi, Jianglin Fan, Masayuki Takeda, Jian Yao
Carbenoxolone (CBX) is a clinically prescribed drug for the treatment of digestive ulcer and inflammation. It is also a widely used pharmacological inhibitor of several channels in basic research. Given that the overactivity of several channels, including those inhibitable by CBX, underlies bladder dysfunction, we tested the potential therapeutic application and mechanism of CBX in the treatment of voiding dysfunction. In a mouse model of cystitis induced by cyclophosphamide (CYP), CBX administration prevented the CYP-elicited increase in bladder weight, oedema, haemorrhage, and urothelial injury...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28242818/characterization-of-flow-regulated-cortical-collecting-duct-endothelin-1-production
#11
Nirupama Ramkumar, Yang Gao, Donald E Kohan
Collecting duct (CD) endothelin-1 (ET-1) is an autocrine inhibitor of Na(+) and water reabsorption. Salt or water loading increases CD ET-1 production; this is likely due, at least in part, to increased tubule fluid flow. The mechanisms by which flow stimulates CD ET-1 production are incompletely understood. In particular, flow induction of cortical CD (CCD) and inner medullary CD (IMCD) ET-1 synthesis may occur via different mechanisms. Since flow-mediated ET-1 production in IMCD has been more extensively characterized than in the CCD, this study was undertaken to further examine putative signaling pathways involved in flow-stimulated CCD ET-1 production...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28239332/characterization-of-the-circumlimbal-suture-model-of-chronic-iop-elevation-in-mice-and-assessment-of-changes-in-gene-expression-of-stretch-sensitive-channels
#12
Da Zhao, Christine T O Nguyen, Vickie H Y Wong, Jeremiah K H Lim, Zheng He, Andrew I Jobling, Erica L Fletcher, Holly R Chinnery, Algis J Vingrys, Bang V Bui
To consider whether a circumlimbal suture can be used to chronically elevate intraocular pressure (IOP) in mice and to assess its effect on retinal structure, function and gene expression of stretch sensitive channels. Anesthetized adult C57BL6/J mice had a circumlimbal suture (10/0) applied around the equator of one eye. In treated eyes (n = 23) the suture was left in place for 12 weeks whilst in sham control eyes the suture was removed at day two (n = 17). Contralateral eyes served as untreated controls. IOP was measured after surgery and once a week thereafter...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28225032/4-isopropylcyclohexanol-has-potential-analgesic-effects-through-the-inhibition-of-anoctamin-1-trpv1-and-trpa1-channel-activities
#13
Yasunori Takayama, Hidemasa Furue, Makoto Tominaga
Interactions between calcium-activated chloride channel anoctamin 1 (ANO1) and transient receptor potential vanilloid 1 (TRPV1) enhance pain sensations in mice, suggesting that ANO1 inhibition could have analgesic effects. Here we show that menthol and the menthol analogue isopropylcyclohexane (iPr-CyH) inhibited ANO1 channels in mice. The iPr-CyH derivative 4-isopropylcyclohexanol (4-iPr-CyH-OH) inhibited mouse ANO1 currents more potently than iPr-CyH. Moreover, 4-iPr-CyH-OH inhibited the activities of TRPV1, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8) and TRPV4...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205608/blockage-of-transient-receptor-potential-vanilloid-4-alleviates-myocardial-ischemia-reperfusion-injury-in-mice
#14
Qian Dong, Jing Li, Qiong-Feng Wu, Ning Zhao, Cheng Qian, Dan Ding, Bin-Bin Wang, Lei Chen, Ke-Fang Guo, Dehao Fu, Bing Han, Yu-Hua Liao, Yi-Mei Du
Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24-72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202366/modulation-of-the-trpv4-ion-channel-as-a-therapeutic-target-for-disease
#15
REVIEW
Megan S Grace, Sara J Bonvini, Maria G Belvisi, Peter McIntyre
Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and pathophysiological processes. TRPV4 knockout mice and several synthetic pharmacological compounds that selectively target TRPV4 are now available, which has allowed detailed investigation in to the therapeutic potential of this ion channel. Results from animal studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28187982/the-renal-trpv4-channel-is-essential-for-adaptation-to-increased-dietary-potassium
#16
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28158279/analysis-of-trpv-channel-activation-by-stimulation-of-fc%C3%AE%C2%B5ri-and-mrgpr-receptors-in-mouse-peritoneal-mast-cells
#17
A Solís-López, U Kriebs, A Marx, S Mannebach, W B Liedtke, M J Caterina, M Freichel, V V Tsvilovskyy
The activation of mast cells (MC) is part of the innate and adaptive immune responses and depends on Ca2+ entry across the plasma membrane, leading to the release of preformed inflammatory mediators by degranulation or by de novo synthesis. The calcium conducting channels of the TRPV family, known by their thermo and osmotic sensitivity, have been proposed to be involved in the MC activation in murine, rat, and human mast cell models. So far, immortalized mast cell lines and nonspecific TRPV blockers have been employed to characterize the role of TRPV channels in MC...
2017: PloS One
https://www.readbyqxmd.com/read/28143892/activation-of-trpv4-by-dietary-apigenin-antagonizes-renal-fibrosis-in-deoxycorticosterone-acetate-doca-salt-induced-hypertension
#18
Xing Wei, Peng Gao, Yunfei Pu, Qiang Li, Tao Yang, Hexuan Zhang, Shiqiang Xiong, Yuanting Cui, Li Li, Xin Ma, Daoyan Liu, Zhiming Zhu
Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remain elusive. In this study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks...
January 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28143710/hepatic-and-renal-mechanisms-underlying-the-osmopressor-response
#19
Tu H Mai, Emily M Garland, André Diedrich, David Robertson
Increased blood pressure (BP) is observed in patients with impaired baroreflexes after water drinking. The stimulus for this effect is low blood osmolality, and it has been termed the osmopressor response (OPR). The BP increase is associated with activation of the sympathetic nervous system and a requirement for transient receptor potential vanilloid 4 (TRPV4) channels. However, the mechanisms underlying the OPR are poorly understood. We tested the hypothesis that hypotonicity is sensed in the portal area to initiate the OPR...
January 27, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28135189/direct-measurement-of-trpv4-and-piezo1-activity-reveals-multiple-mechanotransduction-pathways-in-chondrocytes
#20
M Rocio Servin-Vences, Mirko Moroni, Gary R Lewin, Kate Poole
The joints of mammals are lined with cartilage, comprised of individual chondrocytes embedded in a specialized extracellular matrix. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis. It has been proposed that mechanically gated ion channels are of functional importance in chondrocyte mechanotransduction; however, direct evidence of mechanical current activation in these cells has been lacking. We have used high-speed pressure clamp and elastomeric pillar arrays to apply distinct mechanical stimuli to primary murine chondrocytes, stretch of the membrane and deflection of cell-substrate contacts points, respectively...
January 30, 2017: ELife
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